Dependence of gamma-aminobutyric acid modulation of cholinergic transmission on nitric oxide and purines in cat terminal ileum.
The possible involvement of purines and/or nitric oxide (NO) in the gamma-aminobutyric acid (GABA)A receptor-mediated effects on the spontaneous activity of isolated preparations from longitudinal and circular muscles of cat terminal ileum was investigated. GABA had biphasic effects, which were neurogenic and muscarinic. ATP and adenosine dose dependently inhibited the activity of the muscles. A contractile response evoked by the nucleotide only was also observed. The effects of the purines were equipotent and resistant to Nomega-nitro-L-arginine (L-NNA), tetrodotoxin and to desensitization by alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP), except for the contractile effect of ATP, which was abolished by alpha,beta-meATP. Pretreatment of the preparations with ATP or adenosine produced: (i) desensitization to the effects of the respective purinoceptor agonist only; and (ii) suppression of the GABA-induced responses of longitudinal and circular muscles. Hemoglobin and L-NNA greatly reduced or completely blocked the GABA(A)-induced relaxation and decreased the GABA(A)-induced contraction. Our results indicate that purines and NO, to a different extent, mediate the relaxant phase of the GABA effects in both layers. Interactions between muscarinic cholinoceptors and GABA-nitrergic pathway and a concomitant activation of postjunctional P1 and P2y purinoceptors are suggested to explain the prejunctional biphasic effects of GABA.
Pencheva
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Laboratory of Peripheral Synapses, Institute of Physiology, Bulgarian Academy of Sciences, Sofia. nevena@iph.bio.acad.bg
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D018756:GABA Antagonists / Q000494:pharmacology; D007082:Ileum / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D058913:Purinergic Agonists; D011950:Receptors, Cholinergic / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D011983:Receptors, Purinergic / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000502:physiology
D018756:GABA Antagonists; D058913:Purinergic Agonists; D011950:Receptors, Cholinergic; D018079:Receptors, GABA; D011983:Receptors, Purinergic; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D000241:Adenosine